ELF4 was a prognostic biomarker and related to immune infiltrates in glioma

被引:2
作者
Zhuang, Zhongwei [1 ]
Zhang, Chunyu [2 ]
Tan, Yinqiu [3 ]
Zhang, Jing [2 ,4 ]
Zhong, Chunlong [1 ,2 ]
机构
[1] Nanjing Med Univ, Shanghai East Hosp, Dept Neurosurg, Nanjing, Peoples R China
[2] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Neurosurg, Shanghai, Peoples R China
[3] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurosurg, Wuhan, Peoples R China
[4] Tongji Univ, Inst Adv Study, Shanghai, Peoples R China
基金
上海市自然科学基金; 中国国家自然科学基金;
关键词
glioma; prognosis; immune; GlioVis; scRNA-seq; PROMOTES STEMNESS; T-CELLS; TRANSCRIPTION; SERVER;
D O I
10.7150/jca.96886
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
ELF4 (E74-like factor 4) is a transcription factor, dysregulation of which has been associated with carcinogenesis and cancer development. Nevertheless, the precise role of ELF4 in glioma pathology and its impact on clinical outcomes remains to be investigated. In the present research, comprehensive analyses demonstrated that elevated expression of ELF4 in glioma tissues correlates with malignant phenotypes and adverse clinical outcomes. Multivariate Cox regression analysis determined that ELF4 expression could serve as a reliable predictor of glioma outcomes. (CGGA, hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.09-1.34, p<0.001; TCGA, HR: 1.19, 95%CI: 1.01-1.41, p=0.043; and Gravendeel, HR: 1.44, 95%CI: 1.15-1.80, p=0.002). Knockdown of ELF4 reduced the cell viability and migration capacity of glioma cells in vitro. In addition to the tumor invasive role, enrichment analysis revealed the overexpressed ELF4 was involved in the immune regulation, characterized by the elevated activity of Il6/Jak/Stat3 signaling, interferon alpha (IFN-alpha) response, and IL2/Stat5 signaling. Single-cell RNA sequencing (scRNA)-seq and spatial transcriptome (ST)-seq analyses revealed that ELF4 could induce reprogramming of tumor-associated monocytes/macrophages (TAMMs). Molecular docking analysis revealed ELF4 might be targeted by drugs/compounds, including Veliparib (ABT-888), Motesanib (AMG 706), and EHT 1864. Genomic analysis revealed that, in LGG, in the low ELF4 expression subgroup, IDH1 demonstrated a higher mutation rate, and TP53 and ATRX Chromatin Remodeler (ATRX) displayed the lower mutation rates, than the high ELF4 expression group. Conclusion: Our research suggests that ELF4 may contribute to the prognostic assessment of glioma and personalized medicine.
引用
收藏
页码:5101 / 5117
页数:17
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